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Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat.

Publication ,  Journal Article
Gupta, A; Nines, R; Rodrigo, KA; Aziz, RA; Carlton, PS; Gray, DL; Steele, VE; Morse, MA; Stoner, GD
Published in: J Natl Cancer Inst
July 4, 2001

BACKGROUND: 9-cis-Retinoic acid (9-cis-RA) and N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive agents against epithelial tumors in the oral cavity, breast, and prostate. We tested the inhibitory activity of these retinoids against N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. METHODS: Male Fischer 344 rats were randomly assigned to receive diets either lacking or containing 9-cis-RA or 4-HPR for 1 week before tumor initiation with NMBA and then for the duration of the study. NMBA metabolism, O(6)-methylguanine adduct formation, and cytochrome P450 messenger RNA (mRNA) expression in the esophagi of the rats were studied to investigate the mechanisms by which dietary 4-HPR affects tumorigenesis. All statistical tests were two-sided. RESULTS: Dietary 4-HPR resulted in a dose-dependent and statistically significant enhancement (P<.05) of tumorigenesis in response to NMBA. In two different tumor bioassays, the mean tumor multiplicity for rats fed the highest concentration of dietary 4-HPR (0.8 g/kg diet) was increased by 5.9 tumors (95% confidence interval [CI] = 1.7 to 10.1 tumors) and 6.7 tumors (95% CI = 5.6 to 7.8 tumors) compared with the mean tumor multiplicity for rats that received the control diet lacking 4-HPR. Animals fed diets containing 9-cis-RA displayed no statistically significant increase in tumorigenesis. Compared with animals fed a diet lacking 4-HPR, animals fed 4-HPR had increased NMBA metabolism in esophageal explant cultures and had higher levels of O(6)-methylguanine DNA adducts and CYP2A3 mRNA in their esophagi. CONCLUSIONS: Dietary 4-HPR enhances tumorigenesis in response to NMBA in the rat esophagus by increasing tumor initiation events. Dietary 4-HPR may exert paradoxical effects at some sites, such as the aerodigestive tract, by modulating the bioactivation of carcinogens in target tissues.

Duke Scholars

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

July 4, 2001

Volume

93

Issue

13

Start / End Page

990 / 998

Location

United States

Related Subject Headings

  • Tretinoin
  • Time Factors
  • Retinoids
  • Rats, Inbred F344
  • Rats
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Male
  • Fenretinide
  • Esophagus
 

Citation

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Gupta, A., Nines, R., Rodrigo, K. A., Aziz, R. A., Carlton, P. S., Gray, D. L., … Stoner, G. D. (2001). Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat. J Natl Cancer Inst, 93(13), 990–998. https://doi.org/10.1093/jnci/93.13.990
Gupta, A., R. Nines, K. A. Rodrigo, R. A. Aziz, P. S. Carlton, D. L. Gray, V. E. Steele, M. A. Morse, and G. D. Stoner. “Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat.J Natl Cancer Inst 93, no. 13 (July 4, 2001): 990–98. https://doi.org/10.1093/jnci/93.13.990.
Gupta A, Nines R, Rodrigo KA, Aziz RA, Carlton PS, Gray DL, et al. Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat. J Natl Cancer Inst. 2001 Jul 4;93(13):990–8.
Gupta, A., et al. “Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat.J Natl Cancer Inst, vol. 93, no. 13, July 2001, pp. 990–98. Pubmed, doi:10.1093/jnci/93.13.990.
Gupta A, Nines R, Rodrigo KA, Aziz RA, Carlton PS, Gray DL, Steele VE, Morse MA, Stoner GD. Effects of dietary N-(4-hydroxyphenyl)retinamide on N-nitrosomethylbenzylamine metabolism and esophageal tumorigenesis in the Fischer 344 rat. J Natl Cancer Inst. 2001 Jul 4;93(13):990–998.
Journal cover image

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

July 4, 2001

Volume

93

Issue

13

Start / End Page

990 / 998

Location

United States

Related Subject Headings

  • Tretinoin
  • Time Factors
  • Retinoids
  • Rats, Inbred F344
  • Rats
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Male
  • Fenretinide
  • Esophagus